Droplet forming apparatus for use in producing uniform particles

ABSTRACT

Uniform particles are produced by introducing a laminar stream of a core liquid into a laminar flowing body of an immiscible sheath liquid. The core liquid or the sheath liquid, or both liquids, can contain one or more materials dispersed (dissolved or suspended) in them from which the uniform particles are formed. The two liquids and the dispersed material are expelled from a nozzle to form a liquid jet. The liquid jet is disturbed at a uniform, periodic rate to form liquid droplets which contain a uniform amount of the core liquid, the sheath liquid and the dispersed material. The droplets are collected and held in a catch liquid until the core and the sheath liquid in each droplet have diffused into the catch liquid leaving the uniform particles formed from the dispersed materials. There can be more than one sheath liquid which can also contain one or more materials dispersed in it.

This is a division, of application Ser. No. 679,241, filed Apr. 22, 1976now U.S. Pat. No. 4,162,282.

BACKGROUND OF THE INVENTION

This invention concerns the production of uniform dimensioned particles,and more particularly, novel apparatus and methodology for producinguniform dimensioned spheres of minute sizes from various materials byforming uniform droplets containing uniform amounts of the materials anda uniform amount of a sheath liquid and a uniform amount of a coreliquid immiscible with the sheath liquid.

Minute, spherical particles which are very uniform in volume and whichcan contain a uniform amount of an added material, such as a dye, haveutility in many fields. For example, uniform plastic particles havingknown and controllable physical and optical properties are of great aidin developing instruments for use in biological cell analysis. Theparticles are highly useful also in the testing and calibration of suchinstruments. Particles of uranium oxide and plutonium oxide havinguniform volume provide useful reactor fuel materials. Microspheres ofradioactive materials that are uniform in size and volume are highlydesirable for use in many biological and medical studies including thoseconcerning deposition of various sizes of blood borne particles in thelungs, distribution of fetal blood flow, and distribution of cardiacoutput, for instance.

A uniform particle formed within a particle could be used in lightscatter or other cell studies where a difference in the index ofrefraction between the cytoplasm and the nucleus is important. Byforming a particle within a particle or a particle within a particlewithin a particle, very uniform pseudo-cells can be formed forcalibrating and developing instruments used in these studies.

One system for producing uniform particles is shown in Fulwyler M. J.,U.S. Pat. No. 3,790,492, issued Feb. 5, 1974. In this system, dropletsof core liquid are formed in a laminar, flowing stream of sheath liquid.In utilizing this system it has been found that a small orifice, on theorder of 20 microns in diameter, must be used to inject the core liquidinto the moving stream of sheath liquid. Because of its small size, thenozzle used in this system is subject to plugging by the core liquid.Another limitation found in utilizing this system, is that the coreliquid must be injected into the moving stream of sheath liquidessentially at the relatively low velocity of the sheath liquid toprevent the occurrence of turbulence. This results in a limited rate ofdroplet production on the order of 13,000 droplets per second. The sizerange of the diameters of the particles produced by this system is onthe order of, but not limited to, 2 to 40 microns.

SUMMARY OF THE INVENTION

In practicing a preferred embodiment of the invention, a core liquid isintroduced into a flowing body of an immiscible sheath liquid. Either orboth liquids can have one or more materials dispersed in them. Theliquids and the dispersed material are formed into a liquid jet. Theliquid jet is periodically disturbed to form droplets containing auniform amount of the core liquid, the sheath liquid, and the dispersedmaterial. The droplets can be collected in a catch liquid which isstirred or agitated until a uniform particle is formed.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatic view of a preferred embodiment of the inventionwith portions broken away to show details in a representative manner;

FIG. 1A is an enlarged view of the particle forming portion of FIG. 1;

FIG. 2 is a chart illustrating the degree of uniformity of volume ofrepresentative particles produced by a preferred embodiment of theinvention;

FIG. 3 is a chart illustrating the degree of uniformity of fluorescenceof representative particles produced by a preferred embodiment of theinvention; and

FIG. 4 is an enlarged sectional view of a particle within a particlewithin a particle.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Referring to FIG. 1, a sheath liquid 10 is stored at a desired pressurein a first reservoir 12. The sheath liquid flows under pressure througha first conduit 14 into a flow chamber 16. The sheath liquid 10 flowsaround an injection tube 18 substantially centered in the flow chamber16, becoming a laminar flowing body 19 and is expelled through a firstnozzle 20 as a liquid jet 22. A core liquid 24, immiscible with thesheath liquid 10, is stored at a desired pressure in a second reservoir26. The core liquid 24 flows under pressure through a second conduit 28into the injection tube 18 which extends through one end of the flowchamber 16 to a point adjacent the lower end of the flow chamber. Thecore liquid 24 is expelled through a second nozzle 30 in the end of theinjection tube 18 at the lower end of chamber 16 as a laminar stream 32which is entrained in the liquid jet 22. As the core liquid 24 isimmiscible in the sheath liquid 10, there exists a boundary surfacebetween the two liquids.

The pressure supplied to the first and second reservoirs 12 and 26 canbe supplied from any convenient source, as from a pressure source 21.The pressure can be developed by any well-known method. The pressure issupplied to the first reservoir 12 through a first conduit 23 and to thesecond reservoir 26 through a second conduit 25. The desired pressuresin the respective reservoirs can be obtained by adjusting a first valve27 in the first conduit 23 and a second valve 29 in the second conduit25.

Either the core liquid 24 or the sheath liquid 10 or both of the liquidshave one or more materials dispersed therein, either by solution orsuspension. The operation of the preferred embodiment will be describedfirst with the dispersed material only in the core liquid 24.

A periodic disturbance is imparted to the liquid jet 22 to formdroplets. The periodic disturbance can be generated by thermalmodification of the surface tension of the liquid jet or by a vibrationdevice 34 coupled to the chamber 16 by a rod 36. The vibration device 34can be a suitable piezoelectric crystal device. To form uniformdroplets, the periodic disturbance must be uniform and of a constantfrequency. The frequency can be selected from several resonantfrequencies determined by the velocity and diameter of the liquid jet22. The periodic disturbance of the liquid jet 22 causes a disturbance,indicated diagrammatically at 38, in the liquid jet which causes theliquid jet 22 to separate into uniform droplets shown at 40. As theuniform droplets form, a uniform segment 42 of the core liquid laminarstream 32 is partitioned into each droplet (more clearly illustrated inFIG. 1A). A surface tension exists between the two fluids causing thesegment 42 of core liquid to develop a minimum surface configuration.This minimum surface configuration will be a uniform sphere 44.

The uniform droplets 40 containing the uniform spheres 44 are receivedby a catch liquid 46 contained in a third reservoir 48. The uniformspheres 44 are shielded from the impact with the catch liquid 46 by thesheath liquid surrounding them. The catch liquid 46 is chosen such thatthe core liquid 24 is slightly soluble and will dissolve in it. Thecatch liquid 46 can be stirred or agitated in a conventional manneruntil the sheath liquid and the core liquid 24 of the uniform spheres 44have dissolved in the catch liquid 46. When the core liquid 24 hasdissolved uniform spherical solid particles 50 remain, which can beremoved and concentrated in a conventional manner as by settling,filtering, centrifuging or otherwise.

The diameter of the particles 50 is dependent upon the concentration ofthe dispersed material in the core liquid 24, the volume of the coreliquid 24 emerging in the stream 32, and the rate of the formation ofthe droplets 40.

Utilizing this embodiment of the invention, particles 50 can be formedhaving a diameter in the range of 1 to 100 microns. The particles 50will have approximately a two percent variation in their diameters. Thefirst and second nozzles 20 and 30 can have a diameter of 50 to 100microns. The core liquid 24 can be stored at a pressure of 10 to 30 psi.The sheath liquid 10 can be stored at a pressure of 30 to 60 psi. Thiswill produce flow rates of 0.5 to 1.0 ml/minute and 5 to 10 ml/minuterespectively. The liquid jet 22 can be disturbed at a rate of 25 to 40kilohertz which produces 25 to 40 thousand of the particles/second. Theabove ranges are the preferable ranges of this embodiment of theinvention; however, the invention is not limited to the specific rangesenumerated.

Although the following two examples describe the production of uniformplastic particles, the invention is not limited to this application butcan also be utilized to produce uniform particles of zirconium dioxide,clay, gelatin and other materials.

EXAMPLE I

The apparatus of FIG. 1 was used to produce the uniform particles 50 ofpolystyrene containing a fluorescent dye. The core liquid 24 was 25percent dichloroethane and 75 percent dichloromethane. The dispersed(dissolved) materials in the core liquid were polystyrene (0.06 percentby weight/volume) and the fluorescent dye (0.0009 by weight/volume). Thecore liquid 24 containing the dissolved materials was placed in thereservoir 26 at a pressure of 20 psi. The sheath liquid 10 was anaqueous solution containing 3 percent by volume of a nonionic surfactantand 0.3 percent of a quaternary ammonium chloride biocide, and wasplaced in the reservoir 12 at a pressure 15 psi. At these pressures theflow of the core liquid 24 was approximately 0.6 ml/min and the flow ofthe sheath liquid 10 was 10 ml/min. Once the core and the sheath liquidwere in a laminar flow through the first nozzle 20, the vibration device34 was operated at a frequency of 32,200 hertz.

The resulting droplets 40 were prevented from coalescing by applying anegative charge to each of the droplets 40 as they were formed. Thecharge was applied in a conventional manner as by an electrode 41. Theresulting electrostatic repulsion maintains the separation of thedroplets as they pass through the intervening air between the nozzle 20and the catch liquid 46. The droplets 40 were collected in a beaker 48containing the catch liquid 46 which was an aqueous solution of nonionicsurfactant (4 percent by volume) and quaternary ammonium chloridebiocide (0.8 percent by volume). The core liquid 24 diffused into thecatch liquid 46, leaving the solid polystyrene microspheres 50. Themicrospheres 50 had diameters of 9.8 microns and a coefficient ofvariation in diameter of one percent which is shown in FIG. 2. Thecoefficient of variation in fluorescence intensity of the microspheres50 was four percent as shown in FIG. 3.

EXAMPLE II

The apparatus of FIG. 1 was also used to produce the uniform particles50 of polystyrene containing a blue dye. The core liquid 24 was 24percent dichloroethane, 74.7 percent dichloromethane and 0.4 percentxylene. The dispersed (dissovled) materials in the core liquid werepolystyrene (0.20 percent by weight/volume) and the blue dye (0.005percent by weight/volume). The core liquid 24 containing the dissolvedmaterials was placed in the reservoir 26 at a pressure of 44 psi. Thesheath liquid 10 was an aqueous solution containing 0.63 percent byvolume of nonionic surfactant and 0.25 percent by volume of a quaternaryammonium chloride biocide, and was placed in the reservoir 12 at apressure of 32 psi. At these pressures the flow of the core liquid 24was approximately 1.1 ml/min and the flow of the sheath liquid 10 was 6ml/min. Once the core liquid 24 and the sheath liquid 10 were in alaminar flow through the first nozzle 20, the vibration device 34 wasoperated at a frequency of 35,000 hertz.

The resulting droplets 40 were prevented from coalescing and theirvolocity was dissipated by negatively charging them as they were formed.The droplets 40 were collected in a beaker 48 containing the catchliquid 46 which was an aqueous solution of nonionic surfactant (2.5percent by volume) and quaternary ammonium chloride biocide (1.0 percentby volume). The core liquid 24 diffused into the catch liquid 46,leaving the solid polystyrene microspheres 50 containing the blue dye.The microspheres 50 had diameters of 13.8 micrometers and a coefficientof variation in diameter of 1.3 percent.

The manner of introducing the periodic disturbance to the liquid jet 22is not limited to the vibration device 34. Alternatively, thevibrational energy could be directly coupled into the core liquid 24 orthe sheath liquid 10. Also, the liquid jet 22 could be disturbed afterit has been ejected from the nozzle 20 by vibrational, thermal or otherenergy.

It is a feature of the apparatus that each of the droplets 40 areextremely uniform in the volume of the core liquid 24 and in the volumeof the sheath liquid 10 contained within it. However, it should be notedthat the ratio of the volume of core liquid 24 to the volume of sheathliquid 10 contained in each droplet 40, can be varied in amount asdesired.

The foregoing discussed forming the particles 50 from one or moresuitable materials dispersed in the core liquid 24. However, bydispersing one or more suitable materials in the sheath liquid 10, theparticles 50 can be formed from the sheath material, which also containa droplet of the core liquid 24. In addition, a particle within aparticle can be produced by dispersing one or more suitable materials inthe sheath liquid 10 and the core liquid 24. By selecting suitablematerials in suitable amounts and controlling the volume of core liquid24 and sheath liquid 10 in each droplet 40, it may be feasible toproduce particles with any desired index of refraction between thepseudocytoplasm and the nucleus of each particle. In the theory of thisinvention, the nucleus of the particle may be a liquid or a solid also,as desired.

As shown in FIG. 4, by utilizing a second sheath liquid outside thesheath liquid 10, a particle 52 within a particle 54 within a particle56 can be feasible. A particle 50' is shown in section, with the innerparticle 52 formed from the core liquid; the particle 54 formed from amaterial or materials dispersed in the sheath liquid 10; and theparticle 56 formed from a material or materials dispersed in the secondsheath liquid. Either of the two inner particles 52, 54 may be formedfrom a liquid or they can both be solid particles formed from materialsdispersed in the liquids. By selecting suitable materials and dyes inproper amounts, the index of refraction between each of the particles52, 54, 56 can be varied as well as the respective volumes of eachparticle. Applicants have not produced such complex particles, butbelieve that it may be feasible to do within the concept of theirinvention as set forth herein.

Many modifications and variations of the present invention are possiblein light of the above teachings. It is, therefore, to be understood thatwithin the scope of the appended claims the invention may be practicedotherwise than as specifically described.

What is claimed and desired to be secured by Letters Patent of theUnited States is:
 1. A droplet forming apparatus for producing uniformlysized solid particles from dispersed material in at least one of a coreand sheath liquids which are immiscible with each other and supplied tothe apparatus from a source of said liquids, said apparatuscomprising:means for connecting the source of core liquid to theapparatus; means for connecting the source of sheath liquid to theapparatus; means for forming a moving body of at least one sheath liquidfor laminar movement through the apparatus; means for introducing saidcore liquid as a laminar stream into said moving body at a selectedlocation along the path of movement of the moving body through theapparatus; means for producing a liquid jet from said moving body aftersaid introduction of said core liquid; disturbance means forperiodically disturbing said liquid jet to separate said liquid jetincluding said core and said sheath liquids into unconnected uniformdroplets containing a uniform amount of said disbursed material, saidcore liquid and said sheath liquid; and means to collect said formeddroplets in a catch liquid in which said sheath liquid and said coreliquid are each soluble, whereby said sheath liquid and said core liquidare dissolved therein to render the material dispersed in said coreliquid into said uniformily sized solid particles.
 2. An apparatusaccording to claim 1 wherein said disturbance means includes:means foruniformly and periodically disturbing said liquid jet at a constant ratein a transverse direction thereto.
 3. An apparatus according to claim 1wherein said means for introducing includes:means for introducing saidcore liquid substantially into the center of said moving body of sheathliquid.
 4. An apparatus according to claim 1 wherein said means forintroducing includes:means for introducing said core liquidsubstantially coaxial with the axis of said moving body of sheathliquid.
 5. An apparatus according to claim 1 further including:chargingmeans for applying like-repelling charges to each of said uniformdroplets.